tbuckley/cabot-search huggingface dataset:
Biodegradable Microrobots for DNA Vaccine Delivery
Authors: Shuxun Chen, Zhiwu Tan, Pan Liao, Yanfang Li, Yun Qu, Qi Zhang, Mingxuan Yang, Kannie Wai Yan Chan, Li Zhang, Kwan Man, Zhiwei Chen, Dong Sun
Journal: Advanced Healthcare Materials (2023)

Abstract The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two‐photon polymerization of gelatin methacryloyl (GelMA) and their proof‐of‐concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrate the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.
Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial
Authors: Lameck Chinula, Lauren Ziemba, Sean Brummel, Katie McCarthy, Anne Coletti, Chelsea Krotje, Benjamin Johnston, Kevin Knowles, Sikhulile Moyo, Lynda Stranix-Chibanda, Risa Hoffman, Paul E Sax, Jeffrey Stringer, Nahida Chakhtoura, Patrick Jean-Philippe, Violet Korutaro, Haseena Cassim, Lee Fairlie, Gaerolwe Masheto, Ceejay Boyce, Lisa M Frenkel, K Rivet Amico, Lynette Purdue, Roger Shapiro, Blandina Theophil Mmbaga, Faeezah Patel, Jean van Wyk, James F Rooney, Judith S Currier, Shahin Lockman, Brookie M. Best, Cheryl D Blanchette, Renee Browning, Nagawa Jaliaah, Mark Mirochnick, William A. Murtaugh, Emmanuel Patras, Frances Whalen, Jeremiah D. Momper, Ponego L. Ponatshego, Lesedi Tirelo, Boitshepo J. Seme, Georginah O. Modise, Mpho S. Raesi, Marian E. Budu, Moakanyi Ramogodiri, Ricardo H. Oliveira, Cristina B Hofe, Thalita Fernandes de Abreu, Lorena M. Pestanha, Esaú João, Leon C. Sidi, Trevon Fuller, Maria L.S Cruz, Jorge Pinto, Flãvia Ferreira, Mãrio Correa Jr, Juliana Romeiro, Jose H. Pilotto, Luis E.B.C Fernandes, Luiz F. Moreira, Ivete M. Gomes, Shilpa Naik, Neetal Nevrekar, Vidya Mave, Aarti Kinikar, Elizea Horne, Hamisha Soma-Kasiram, Avy Violari, Sisinyana R. Mathiba, Mandisa Nyati, Gerhard Theron, Jeanne de Jager, Magdel Rossouw, Lindie Rossouw, Sherika Hanley, Alicia C. Desmond, Rosemary Gazu, Vani Govender, Amphan Chalermchockcharoenkit, Manopchai Thamkhantho, Peerawong Werarak, Supattra Rungmaitree, Jullapong Achalapong, Lukkana Sitiritkawin, Tim R. Cressey, Pra-ornsuda Sukrakanchana, Linda Aurpibul, Fuanglada Tongprasert, Chintana Khamrong, Sopida Kiattivej, Deo Wabwire, Enid Kabugo, Joel Maena, Frances Nakayiwa, Victoria Ndyanabangi, Beatrice Nagaddya, Rogers Sekabira, Justus Ashaba, Charles D. Mitchell, Adriana Drada, Grace A. Alvarez, Gwendolyn B. Scott, Mobeen Rathore, Saniyyah Mahmoudi, Adnan Shabbir, Nizar Maraqa, Patricia F. Mandima, Mercy Mutambanengwe, Suzen Maonera, Gift Chareka, Teacler Nematadzira, Vongai Chanaiwa, Taguma A. Matubu, Kevin Tamirepi, Sukunena Maturure, Tsungai Mhembere, Tichaona Vhembo, Tinashe Chidemo, Frances Whalen
Journal: The Lancet HIV (2023)
Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group
Authors: Atsushi Sato, Yoshihiro Hatta, Chihaya Imai, Koichi Oshima, Yasuhiro Okamoto, Takao Deguchi, Yoshiko Hashii, Takashi Fukushima, Toshinori Hori, Nobutaka Kiyokawa, Motohiro Kato, Shoji Saito, Kenichi Anami, Tatsuhiro Sakamoto, Yoshiyuki Kosaka, Souichi Suenobu, Toshihiko Imamura, Akiko Kada, Akiko M Saito, Atsushi Manabe, Hitoshi Kiyoi, Itaru Matsumura, Katsuyoshi Koh, Arata Watanabe, Yasushi Miyazaki, Keizo Horibe
Journal: The Lancet Haematology (2023)
The ethical, economic, and developmental imperative to prevent small vulnerable newborns and stillbirths: essential actions to improve the country and global response
Authors: Abdu Mohiddin, Katherine E A Semrau, Jonathon Simon, Etienne V Langlois, Jeremy Shiffman, Helen Nabwera, G Justus Hofmeyr, Joy E Lawn, Robert E Black, Sufia Askari, Nigel Klein, Ulla Ashorn, Per Ashorn, Marleen Temmerman
Journal: The Lancet (2023)
Pirtobrutinib: A New Hope for patients with BTK-inhibitor refractory lymphoproliferative disorders
Authors: Philip A Thompson, Constantine Tam
Journal: Blood (2023)

Patients with lymphoproliferative disorders such as CLL and Mantle Cell Lymphoma (MCL) who are resistant to covalent BTK inhibitors (cBTKi), especially if also venetoclax-refractory, have an unmet therapeutic need. Pirtobrutinib, a non-covalent BTK inhibitor, achieves high response rates in cBTKi refractory patients regardless of mechanism of cBTKi resistance. This led to recent accelerated FDA approval in MCL. The toxicity profile in early studies suggests suitability for use in combination approaches. We summarize existing pre-clinical and clinical data with pirtobrutinib.
Annals Graphic Medicine - Pre Scrub
Authors: George M. Anderson
Journal: Annals of Internal Medicine (2023)

Web ExclusivesMay 2023Annals Graphic Medicine - Pre ScrubFREEGeorge M. AndersonGeorge M. AndersonWarren Alpert Medical School of Brown University, Providence, Rhode Island (G.M.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0043 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: George M. AndersonAffiliations: Warren Alpert Medical School of Brown University, Providence, Rhode Island (G.M.A.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0043.Author/Illustrator Information: George M. Anderson is a third-year medical student at the Warren Alpert School of Medicine at Brown University. To see more of his artwork, visit www.georgemanderson.com (e-mail, [email protected]edu).This article was published at Annals.org on 9 May 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics May 2023Volume 176, Issue 5 ePublished: 9 May 2023 Issue Published: May 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Population Genomic Screening for Three Common Hereditary Conditions
Authors: Gregory F. Guzauskas, Shawn Garbett, Zilu Zhou, Jonathan S. Schildcrout, John A. Graves, Marc S. Williams, Jing Hao, Laney K. Jones, Scott J. Spencer, Shangqing Jiang, David L. Veenstra, Josh F. Peterson
Journal: Annals of Internal Medicine (2023)

The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).Decision analytic Markov model.Published literature.Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.Lifetime.U.S. health care payer.Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.National Human Genome Research Institute.
Care of the Patient With Abnormal Kidney Test Results
Authors: Delphine S. Tuot, Neil R. Powe
Journal: Annals of Internal Medicine (2023)

Blood and urine tests are commonly performed by clinicians in both ambulatory and hospital settings that detect chronic and acute kidney disease. Thresholds for these tests have been established that signal the presence and severity of kidney injury or dysfunction. In the appropriate clinical context of a patient's history and physical examination, an abnormal test result should trigger specific actions for clinicians, including reviewing patient medication use, follow-up testing, prescribing lifestyle modifications, and specialist referral. Tests for kidney disease can also be used to determine the future risk for kidney failure as well as cardiovascular death.
Primary Occurrence of Cardiovascular Events After Adding Sodium–Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes
Authors: Tadarro L. Richardson, Alese E. Halvorson, Amber J. Hackstadt, Adriana M. Hung, Robert Greevy, Carlos G. Grijalva, Tom A. Elasy, Christianne L. Roumie
Journal: Annals of Internal Medicine (2023)

Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease. Objective: To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention. Design: Retrospective cohort study of U.S. veterans from 2001 to 2019. Setting: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. Patients: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. Measurements: Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates. Results: The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium–glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [−1.12 to 3.32]) compared with DPP4i. Limitation: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. Conclusion: The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention. Primary Funding Source: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.
Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Akriti Jain, Kendra Sweet
Journal: Journal of the National Comprehensive Cancer Network (2023)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. BPDCN is most often characterized by its presentation with distinct cutaneous lesions. Bone marrow involvement, lymphadenopathy, splenomegaly, and/or cytopenias are also seen to varying degrees. BPDCN presents with diffuse, monomorphous blasts with irregular nuclei, fine chromatin, and scant, agranular cytoplasm. Expression of CD4, CD56, and CD123 is the hallmark of BPDCN. The presence of ≥4 of CD4, CD56, CD123, TCL1, TCF4, and CD303 is necessary for the diagnosis of BPDCN. Prior to December 2018, management of BPDCN revolved around intensive chemotherapy using acute myeloid leukemia or acute lymphoblastic leukemia regimens. However, responses were transient with poor overall survival (OS). Allogeneic stem cell transplantation (alloSCT) is the only potentially curative treatment for BPDCN. Even so, only a minority of patients are candidates for alloSCT given the preponderance of disease in older individuals. For the few fit patients who are candidates for alloSCT, the aim is to achieve complete remission prior to alloSCT. Tagraxofusp (SL-401), a recombinant fusion protein containing interleukin-3 fused to truncated diphtheria toxin, was the first approved CD123-targeted therapy for BPDCN based on a phase I/II clinical trial showing a 90% overall response rate. It was approved by the FDA on December 21, 2018. Capillary leak syndrome is an important adverse effect of tagraxofusp that requires close monitoring. Several clinical trials are underway to study other regimens for the treatment of BPDCN, including IMGN632 (pivekimab sunirine), venetoclax (alone and in combination with hypomethylating agents), CAR-T cells, and bispecific monoclonal antibodies.
Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy
Authors: Justine Lequesne, Florence Joly, Julien Peron, Isabelle Ray-Coquard, Anne-Claire Hardy-Bessard, Frédéric Selle, Dominique Berton, Philippe Follana, Michel Fabbro, Alain Lortholary, Eric Pujade-Lauraine, Sophie Lefèvre-Arbogast, Elodie Coquan
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients’ quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation. Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression. Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P &lt;.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, –3.42 to –3.13; all P &lt;.01). Degrees of association were lower when considering the AE duration. Conclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.
Applying Quality Indicators to Examine Quality of Care During Active Surveillance in Low-Risk Prostate Cancer: A Population-Based Study
Authors: Narhari Timilshina, Antonio Finelli, George Tomlinson, Beate Sander, Shabbir M.H. Alibhai
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Although a few studies have reported wide variations in quality of care in active surveillance (AS), there is a lack of research using validated quality indicators (QIs). The aim of this study was to apply evidence-based QIs to examine the quality of AS care at the population level. Methods: QIs were measured using a population-based retrospective cohort of patients with low-risk prostate cancer diagnosed between 2002 and 2014. We developed 20 QIs through a modified Delphi approach with clinicians targeting the quality of AS care at the population level. QIs included structure (n=1), process of care (n=13), and outcome indicators (n=6). Abstracted pathology data were linked to cancer registry and administrative databases in Ontario, Canada. A total of 17 of 20 QIs could be applied based on available information in administrative databases. Variations in QI performance were explored according to patient age, year of diagnosis, and physician volume. Results: The cohort included 33,454 men with low-risk prostate cancer, with a median age of 65 years (IQR, 59–71 years) and a median prostate-specific antigen level of 6.2 ng/mL. Compliance varied widely for 10 process QIs (range, 36.6%–100.0%, with 6 [60%] QIs &gt;80%). Initial AS uptake was 36.6% and increased over time. Among outcome indicators, significant variations were observed by patient age group (10-year metastasis-free survival was 95.0% for age 65–74 years and 97.5% in age &lt;55 years) and physician average annual AS volume (10-year metastasis-free survival was 94.5% for physicians with 1–2 patients with AS and 95.8% for those with ≥6 patients with AS annually). Conclusions: This study establishes a foundation for quality-of-care assessments and monitoring during AS implementation at a population level. Considerable variations appeared with QIs related to process of care by physician volume and Qis related to outcome by patient age group. These findings may represent areas for targeted quality improvement initiatives.
Are NCI Cancer Centers Providing Adolescents and Young Adults With Cancer Focused Clinical Services? A National Survey
Authors: Katherine Daunov, Michael Daunov, Kara Noskoff, Hilary Gan, Simon Davies, Megan Farrell, Whitney Hadley, Amelia Baffa, Jennifer Giesel, Rachel Egler, Alex Y. Huang, John J. Letterio, Richard T. Lee
Journal: Journal of the National Comprehensive Cancer Network (2023)

This study sought to evaluate the current services and delivery models of adolescent and young adult oncology (AYAO)-specific programs at NCI-designated Cancer Centers (NCI-CCs).NCI, academic, and community cancer centers were electronically sent surveys from October to December 2020 and administered via REDCap.Survey responses were received from 50 of 64 (78%) NCI-CCs, primarily completed by pediatric oncologists (53%), adult oncologists (11%), and social workers (11%). Half (51%) reported an existing AYAO program, with most (66%) started within the past 5 years. Although most programs combined medical and pediatric oncology (59%), 24% were embedded within pediatrics alone. Most programs saw patients aged 15 (55%) to 39 years (66%) mainly via outpatient clinic consultation (93%). Most centers reported access to a range of medical oncology and supportive services, but dedicated services specifically for adolescent and young adults (AYAs) were available at a much lower extent, such as social work (98% vs 58%) and psychology (95% vs 54%). Although fertility preservation was offered by all programs (100%), only two-thirds of NCI centers (64%) reported providing sexual health services to AYAs. Most NCI-CCs (98%) were affiliated with a research consortium, and a lesser extent (73%) reported collaboration between adult and pediatric researchers. Nearly two-thirds (60%) reported that AYA oncology care was important/very important to their respective institution and reported providing good/excellent care to AYAs with cancer (59%), but to a lesser extent reported good/excellent research (36%), sexual health (23%), and education of staff (21%).Results of this first-ever national survey to assess AYAO programs showed that only half of NCI-CCs report having a dedicated AYAO program, and that areas of improvement include staff education, research, and sexual health services for patients.
NCCN Policy Summit: Cancer Care in the Workplace: Building a 21st Century Workplace for Patients, Survivors, and Caretakers
Authors: Victoria Hood, Lindsey Bandini, Taneal Carter, Alyssa Schatz, John Sweetenham, Warren Smedley, Joanna Fawzy Morales, Rebecca V. Nellis, Randy A. Jones, Lynn Zonakis, Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2023)

Survival rates for people with cancer and quality of life for survivors have increased significantly as a result of innovations in cancer treatment, improvements in early detection, and improved healthcare access. In the United States, 1 in 2 men and 1 in 3 women will be diagnosed with cancer in their lifetime. As more cancer survivors and patients remain in the workforce, employers must evaluate how they can adjust workplace policies to meet employee and business needs. Unfortunately, many people still encounter barriers to remaining in the workplace following a cancer diagnosis for themselves or a loved one. In an effort to explore the impacts of contemporary employment policies on patients with cancer, cancer survivors, and caregivers, NCCN hosted the Policy Summit “Cancer Care in the Workplace: Building a 21st Century Workplace for Cancer Patients, Survivors, and Caretakers” on June 17, 2022. This hybrid event, through keynotes and multistakeholder panel discussions, explored issues regarding employer benefit design, policy solutions, current best and promising practices for return to work, and how these issues impact treatment, survivorship, and caregiving in the cancer community.